Immediately alleviating a pain of which a patient with a disease or disorder complains is most important to most of the treatment for the disease or disorder in terms of the mitigation of the patient's physical pain as well as mental anguish. Pain is usually classified into acute pain and chronic pain. The acute pain results from a tissue damage caused by a stimulation such as a mechanical stimulus or heat. Heretofore, all of analgesic agents have been developed with the aim of alleviating the acute pain. The chronic pain means that a pain continuing for 6 or more months, which appears after a recovery of a tissue damage resulting in acute pain or due to lumbago, migraine, arthritis, cancer, and other factors and hinders patient's daily life, or which results from an unknown origin. Moreover, pain is classified into four categories according to the cause: nociceptive, inflammatory, neuropathic (or neurogenic), and psychogenic pains. These pains are treated depending on the respective causes thereof. For example, the invasive pain can completely subside by morphine or the like. The inflammatory pain can cease after inhibition or elimination of the cause using an anti-inflammatory agent. However, it is difficult to remove the neuropathic pain since the cause of the pain is specific. Specifically, the cause of the neuropathic pain is a temporary injury to the nervous system or an abnormal function of the nervous system. That is, the nerve itself has a trouble, and the plasticity in the nervous system becomes chronic. In addition, since the chronic pain induces a new plastic change in the neural circuit, it is difficult to remit the symptom, to say nothing of the cause. The neuropathic pain is a pain as represented by a sensuous expression such as “numbness” or “a shooting pain” and is also a continuous or sudden pain. Moreover, the neuropathic pain is known for its resistance to an antiphlogistic analgesic agent or a narcotic analgesic agent.
The effective method for treating the neuropathic pain includes, for example, methods described in Folia Pharmacol. Jpn., 122, 192-200 (2003) (Non-patent Document 1). In this document, treatments with an α2 adrenergic receptor antagonist, a sodium receptor antagonist, a capsaicin cream, a TrkB receptor inhibitor, or an Rho inhibitor have been examined.
Moreover, Japanese Patent Application Laid-Open No. 535833/2003 (JP-2003-535833A, Patent Document 1) discloses that a pharmaceutical composition containing a kappa-opioid (nalbuphine) and an opioid antagonist (naloxone, naltrexone, nalmefene) is useful for treating a pain including both inflammatory and neuropathic pains. Incidentally, the document does not disclose that a propionic acid-derived nonsteroidal anti-inflammatory agent and a non-pyrazolone antipyretic analgesic agent is further added or mixed to or with the pharmaceutical composition.
Further, Japanese Patent Application Laid-Open No. 512081/1999 (JP-11-512081A, Patent Document 2) discloses that a pharmaceutical composition containing an opioid analgesic agent (such as codeine or dihydrocodeine) as a first component, a nonopioid analgesic agent (such as acetaminophen or ibuprofen) as a second component, an N-methyl-D-aspartate receptor antagonist (such as dextromethorphan) as a third component is useful for treating an acute or chronic pain (e.g., arthritic pain, lumbosacral, musculoskeletal pain, post-operative pain, and headache).
As described above, a variety of treatments for pain has been carried out. However, preparations or treatment methods which enable more effective alleviation and treatment for pain is desired still now. In particular, there are few reports concerning effective treatment methods for a neuropathic pain, which is one of chronic pains, and the development of methods for treating the neuropathic pain effectively has been desired.
[Patent Document 1] JP-2003-535833A (Claims 1, 8, and 9, paragraph number [0002])
[Patent Document 2] JP-11-512081A (Claims 1 and 15, page 8, lines 27-28 of Specification)
[Non-patent Document 1] Folia Pharmacol. Jpn. 122, 192-200 (2003), attributed to Ueda Hiroshi